The underlying theme of this program is to integrate discovery of novel biologically active natural products from organisms that inhabit unique ecological niches with mechanism-directed cancer biology. The overall goal is the identification of clinically useful drugs that target human solid tumor diseases and related infections caused by immune deficiency. The PI, Dr. Ireland will be responsible for administration of the program, including financial management, orchestrating communication between the groups and dissemination of data, tracking of priority leads and arranging meetings with NIH officials. Dr. Ireland will also oversee a natural products subprogram for studies of the chemistry of marine invertebrate animals and associated microorganisms. Dr. Kramer will be responsible for the drug development aspect of this program. This will include initial testing of samples supplied by the natural products groups in Cyanamid's Oncology Drug Screen (CODS), mechanism of action studies, animal toxicology and in vivo antitumor studies in animal models. Dr. Kramer will also oversee testing of samples in immune stimulation assays. Dr. Maiese will oversee a subprogram for studies of marine micro- organisms. Particular emphasis will be placed on micro-organisms obtained from specific environments. Dr. Maiese's group will be responsible for isolation, taxonomic identification and fermentation of subject micro-organisms. Dr. Clardy will oversee a natural products subprogram for studies of novel endophytic fungi and a smaller effort on the characterization of leads by X-ray diffraction. Dr. Andersen will oversee a natural products subprogram for studies of marine invertebrate animals and associated microorganisms.